Background: Recent studies suggest that smoking increases breast cancer risk, and obesity is an established risk factor for postmenopausal breast cancer. Since there is a complex relation between smoking, weight and fat distribution, we hypothesized that the effect of smoking on breast cancer risk may be modified by obesity among postmenopausal women.

Methods: 76,628 women with no previous history of cancer aged 50-79 enrolled in the Women’s Health Initiative Observational Study were recruited at 40 centers across the United States from 1993 to 1998, and were followed up through 2009. Cox proportional hazards regression models estimated hazard ratios (HRs) for invasive breast cancer risk associated with smoking, stratified by obesity status, and adjusting for other breast cancer risk factors. Interactions between obesity status and different metrics of smoking were tested by entering multiplicative interaction terms into the model.

Results: 3,378 incident cases of invasive breast were identified. A significant association between smoking and breast cancer risk was noted in non-obese women, but not in obese women defined by BMI > 30 (p for interaction=0.047). A significantly higher breast cancer risk was observed in non-obese women with long duration of smoking, but not in obese women (p for interaction = 0.03). Similar results were obtained when obesity status was defined by waist circumference > 88 cm.

Conclusion: Our study suggests the effect of smoking on breast cancer risk was modified by obesity among post-menopausal women. The modification effect did not differ by general vs. abdominal obesity.